5’3’TTR-RB15

TTR-RB15 monomer, 2490 nt

TTR-RB155’3’

Self-complementaryTTR-RB15 dimer, 4856 nt

(A) pAAV2-TTR-RB15(used as marker) scAAV2-TTR-RB15

Dimer, 4856 nt

Monomer, 2490 ntParent, 3967 nt

Not-digested

(B)

days 1 1 1 13 3 3 3

HepG2

Parent sc

RB15scR

B15-

mutant

RT-PCR PCR

1 1 1 13 3 3 3

HepG2

Parent sc

RB15scR

B15-

mutant

RB15

(C)

(D)

Apo

B m

RN

A in

Hep

G2

(% o

f in

acti

ve R

B15

-mut

ant)

Ad- RB1 5

-mutant

Ad-RB15

Parent

- AAV2-TTR

-RB1 5-mut ant

scAAV2-TTR

-RB15

scAAV2-TTR

-RB15-mutant

0

25

50

75

100

125

Parent-AAV2

-TTR-RB15

P=0.005 P=0.001ns